SCN5A Variant G274C
Summary of observed carriers, functional annotations, and structural context for SCN5A G274C. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
18%
1/11 effective observations
Estimated BrS1 penetrance
19%
2/11 effective observations
Total carriers
1
0 BrS1 · 0 LQT3 · 1 unaffected
Variant features alone are equivalent to phenotyping 2 individuals for Brugada syndrome and 1 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -8.78 | 1 | 0.56 | 0.977 | 22 | 16 |
PROVEAN scores below -2 suggest deleterious impact. REVEL scores above 0.5–0.75 are often interpreted as likely pathogenic. PolyPhen-2 scores above 0.85 are typically pathogenic. Penetrance density summarises neighbouring residue risk (Kroncke et al. 2019).
Reported carrier data
| Source | Year | Carriers | Unaffected | LQT3 | BrS1 | Other | Other Disease |
|---|---|---|---|---|---|---|---|
| Literature, cohort, and gnomAD | – | 1 | 1 | 0 | 0 | – | |
| Variant features alone | – | 15 | 12 | 1 | 2 | – | – |
Totals may differ from individual publications due to duplicate patients removed during curation.
Nearby variants
Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.
| Neighbour residue | Distance (Å) | Observed variants |
|---|---|---|
| 328 | 13 | |
| 364 | 14 | |
| 277 | 4 | |
| 271 | 10 | L271V, |
| 266 | 14 | L266H, |
| 326 | 13 | |
| 276 | 5 | L276Q, L276P, |
| 348 | 11 | P348A, |
| 270 | 10 | Q270K, |
| 360 | 13 | |
| 279 | 10 | |
| 385 | 10 | A385T, |
| 1552 | 13 | Q1552R, Q1552L, |
| 355 | 8 | F355I, F355C, |
| 1549 | 10 | |
| 278 | 6 | H278D, H278R, |
| 356 | 7 | D356N, |
| 361 | 12 | |
| 343 | 6 | |
| 327 | 12 | |
| 384 | 9 | S384T, |
| 354 | 7 | |
| 329 | 14 | |
| 386 | 13 | G386R, G386R, G386E, |
| 349 | 15 | D349N, |
| 267 | 14 | |
| 1550 | 6 | |
| 357 | 11 | |
| 272 | 7 | |
| 341 | 11 | C341Y, |
| 274 | 0 | G274C, |
| 273 | 5 | |
| 325 | 11 | L325R, |
| 392 | 15 | |
| 324 | 15 | |
| 389 | 13 | Y389H, Y389X, |
| 269 | 9 | |
| 1620 | 14 | T1620K, T1620M, |
| 345 | 10 | |
| 275 | 4 | N275K, N275K, |
| 383 | 14 | |
| 280 | 14 | C280Y, |
| 323 | 14 | |
| 347 | 9 | |
| 382 | 14 | |
| 1548 | 12 | E1548K, G1548K, |
| 351 | 12 | G351S, G351C, G351D, G351V, |
| 265 | 14 | A265V, |
| 1619 | 15 | P1619Q, P1619L, c.4856delC, |
| 358 | 14 | |
| 342 | 11 | |
| 1551 | 9 | D1551N, D1551Y, |
| 346 | 11 | E346K, E346G, E346X, E346D, E346D, |
| 359 | 14 | A359T, p.A359PfsX12, |
| 344 | 9 | A344S, |
| 381 | 10 | c.1140+1G>A, c.1141-3C>A, |
| 352 | 14 | Y352C, |
| 380 | 12 | |
| 268 | 10 | G268S, |
| 377 | 13 | |
| 281 | 15 | V281M, |
| 353 | 10 | T353I, |
| 1623 | 14 | c.4867delC, R1623X, R1623Q, R1623L |